Device for processing a liquid medium comprising cells

ABSTRACT

The invention relates to a device for processing an initial liquid medium ( 4 ) comprising cells in an initial concentration in order to obtain a product liquid medium ( 4 ′) comprising cells in a product concentration, the device ( 2 ) comprising a separator ( 6 ) adapted to separate the initial liquid medium ( 4 ) into various constituents, a first supply system ( 8 ) for supplying the initial liquid medium ( 4 ) to the separator ( 6 ), a first outlet system ( 12 ) for extracting the product liquid medium ( 4 ′) from the separator ( 6 ), a sensor ( 22, 22 ′) adapted to measure a physical parameter related to the concentration of the cells in the initial or product liquid medium ( 4, 4 ′), and a control unit ( 24 ) coupled to the sensor ( 22, 22 ′) and adapted to control at least one process of the device ( 2 ) as a function of the physical parameter measured by the sensor ( 22, 22 ′). The device is characterized by a second supply system ( 10 ) for supplying a solution ( 18 ) to the separator ( 6 ) with a given flow rate. The flow rate of the solution ( 18 ) in the second supply system ( 10 ) during its supply to the separator ( 6 ) is determined based on the at least one process parameter.

The invention relates to a device and method for processing an initialliquid medium comprising cells in an initial concentration in order toobtain a product liquid medium comprising cells in a productconcentration according to the preamble of claim 1 or claim 13,respectively. The cells might be living cells.

Such devices and corresponding methods are known from the prior art. Thedevices typically comprise a separator adapted to separate the initialliquid medium into various constituents, a first supply system forsupplying the initial liquid medium to the separator, a first outletsystem for extracting the product liquid medium from the separator, asensor adapted to measure a physical parameter related to theconcentration of the cells in the initial or product liquid medium, anda control unit coupled to the sensor and adapted to control at least oneprocess parameter of the device as a function of the physical parametermeasured by the sensor.

Such devices are typically used for separating blood into variousconstituents, in particular for extracting red blood cells(erythrocytes) as described for example in EP 0 528 238 B1. The knowndevice for the separation of blood into various constituents is adaptedfor in-vivo-processing, in particular for intraoperative bloodprocessing and comprises a separator which has one intake line with apump and a discharge line for the erythrocyte fraction. To control thepump of the intake line, a sensor for a continuous measurement of thehematocrit value is provided in the intake line. The measured hematocritvalue serves as an input for regulating means. The output of thatregulating means is used to adjust the blood flow through the pumpdepending on the measured hematocrit signal.

It is an object of the present invention to improve such device suchthat it can be used for in vivo and in vitro processing of an initialliquid medium comprising cells in an initial concentration to obtain aproduct liquid medium comprising cells in a product concentration.

According to claim 1, a second supply system for supplying a solutionwith a given flow rate to the separator is provided. The solution isused for processing the initial liquid medium and is washed out toobtain the product liquid medium. For example, the solution can be awashing solution, such as a physiologic saline solution, a cell culturemedium, plasma, albumin or the like. The flow rate of the solution inthe second supply system during its supply to the separator isdetermined by the at least one process parameter of the device that iscontrolled by the control unit coupled to the sensor. In particular, thecontrol unit can be configured such that it reduces the flow rate of thesolution in the second supply system if the concentration of the cellsmeasured in the initial liquid medium increases. While in vivoprocessing requires substantially the same flow rate of the solution inthe second supply system, this flow rate for in vitro processing mayvary depending on the processing speed or the quality of the productliquid medium desired. In particular, the possibility to vary the flowrate of the second supply system enables the device to operate in vitro.

In addition to the flow rate of the solution in the second supplysystem, the process parameter to be controlled by the control unit canalso determine the flow rate of the initial liquid medium in the firstsupply system during its supply to the separator and/or the flow rate ofthe product liquid medium in the first outlet system during itsextraction from the separator. The control unit can be configured tocontrol the flow rate of the initial liquid medium such as to beindirectly proportional to the initial concentration of the cells in theinitial liquid medium in the first supply system. The flow rate of theproduct liquid medium can also be controlled such as to be directlyproportional to the initial concentration of the cells in the initialliquid medium in the first supply system.

According to one aspect of the invention, the separator is a centrifugethat is adapted to separate the initial liquid medium into variousconstituents. The centrifuge can be designed as a planar spiral channel.Alternatively, the centrifuge may be a bell shaped bowl. The processparameter may be used to control the rotational speed of the centrifuge.Preferably, the control unit is configured to control the rotationalspeed such as to be indirectly proportional to the initial concentrationof the cells in the initial liquid medium in the first supply system.The separator can operate continuously or discontinuously (batch wise).

Alternatively, the separator can be a membrane, such as a spinningmembrane, a flat sheet membrane or a hollow fiber membrane.

The first supply system comprises a supply line through which theinitial liquid medium flows into the separator. Correspondingly, thefirst outlet system comprises an output line through which the productliquid medium flows out of the separator. In case that the sensormeasures a physical parameter related to the initial concentration ofthe cells in the initial liquid medium, the measurement is preferablyperformed for the initial liquid medium that is present in the supplyline of the first supply system. In case that the sensor measures aphysical parameter related to the product concentration of the cells inthe product liquid medium, the measurement is preferably performed forthe product liquid medium that is present in the output line of thefirst outlet system.

In order to obtain a product liquid medium of essentially constantquality with respect to the concentration of cells, the control unit canbe configured to control the at least one process parameter of thedevice such that the product concentration of the cells in the productliquid medium is within a predefined range of concentration.Alternatively, the control unit can be configured to control the atleast one process parameter of the device such as to maximize theproduct concentration of the cells in the product liquid medium.

According to another embodiment, the device comprises two sensors, afirst sensor being adapted to measure a physical parameter related tothe concentration of the cells in the initial liquid medium and a secondsensor adapted to measure a physical parameter related to theconcentration of the cells in the product liquid medium.

Claim 13 and its dependent claims refer to a method for processing aninitial liquid medium comprising cells in an initial concentration inorder to obtain a product liquid medium comprising cells in a productconcentration.

The idea underlying the invention shall subsequently be described inmore detail with reference to the embodiments shown in the figures.Herein,

FIG. 1 shows a schematic view of a device for processing a liquid mediumcomprising cells according to a first embodiment of the invention;

FIG. 2 shows a schematic view of a device for processing a liquid mediumcomprising cells according to a second embodiment of the invention; and

FIG. 3 shows a schematic view of a device for processing a liquid mediumcomprising cells according to a third embodiment of the invention.

FIG. 1 shows a first embodiment of a device 2 for processing an initialliquid medium 4 comprising cells in an initial concentration to obtain aproduct liquid medium 4′ comprising cells in a product concentration.The product concentration is intended to be higher than the initialconcentration. As an example, said initial liquid medium 4 can be bloodcomprising blood cells (mainly red blood cells, but also white bloodcells and platelets) and plasma. Here, the cells of interest shall bethe red blood cells, also referred to as erythrocytes. The volumepercentage of red blood cells in blood is referred to as hematocrit. Theproduct liquid medium 4′ shall be the erythrocyte fraction separatedfrom the blood. Furthermore, the initial liquid medium 4 can comprisemajor proportions of rinsing solution, fat, debris and/or particularcomponents such as tissue, small bone particles or the like. Theseadditional components can strongly reduce the hematocrit value for theincoming blood 4.

The device 2 is adapted to process the initial liquid medium 4 in vivoand in particular also in vitro. It comprises a separator 6 that isconnected to two supply systems 8, 10 and two outlet systems 12, 14.

The separator 6 of the embodiment shown in FIG. 1 is a centrifuge. Theseparator 6 comprises a separation chamber 16 being rotatable about anaxis A of rotation and a drive unit (not shown). The preferred directionof rotation of the separator 6 shown in FIG. 1 is counterclockwise andindicated in FIG. 1 by an arrow R. However, the direction of rotationmay also be inverse.

The separation chamber 16 can be a disposable part made from(transparent) plastic material. The separation chamber 16 is designed asan essentially planar spiral channel that winds around the axis A ofrotation, with an increasing distance between the channel and the axis Aalong the direction of rotation R. The separator 6 comprises a volume of185 ml. Alternatively, other volumes may be used.

The first supply system 8 is adapted to supply the initial liquid medium4 to be processed (blood) to the separator 6. The first supply system 8comprises a reservoir 8 a that is connected to the innermost end of thespiral channel of the separator 6 (closest to the axis A) via a supplyline 8 b. The supply line 8 b comprises an adjustable pump 8 c that isadapted to adjust the flow rate of the initial liquid medium 4 from thereservoir 8 a through the supply line 8 b to the separator 6.

The first outlet system 12 is adapted to extract the product liquidmedium 4′ (erythrocyte fraction) from the separator 6 after processingthe initial liquid medium 4. The first outlet system 12 comprises areservoir 12 a that is connected to the outermost end of the spiralformchannel of the separator 6 (furthest away from the axis A) via an outputline 12 b. The output line 12 b comprises an adjustable pump 12 c thatis adapted to adjust the flow rate of the product liquid medium 4′ fromthe separator 6 through the output line 12 b to the reservoir 12 a.

The second supply system 10 is adapted to supply a washing solution 18to the separator 6. The washing solution 18 can be a physiologic salinesolution and is provided to the separator 6 in order to resuspend thecells during processing of the liquid medium 4. In principle the washingsolution 18 can be any medium adapted to host cells. For example themedium may be a cell culture medium, plasma, albumin or the like. Thesecond supply system 10 comprises a reservoir 10 a that is connected tothe separator 6 via a supply line 10 b. The supply line 10 b reaches thespiral channel of the separator 6 preferably about 90-180° before itsoutermost end. In general, the position where the supply line 10 breaches the spiral channel is chosen such as to ensure a sufficientseparation time for the initial liquid medium 4. Therefore, the supplyline 10 b should reach the spiral channel not too close to the outputline 12 b through which the product liquid medium 4′ leaves theseparator 6 in order to allow the cells to separate or settle down againafter the washing step so that the required quality of the productliquid medium 4′ can be obtained. Depending on the type of initialliquid medium 4 to be processed and on the type of cells, the positionwhere the supply line 10 b reaches the spiral channel can vary. Thesupply line 10 b comprises an adjustable pump 10 c that is adapted toadjust the flow rate of the washing solution 18 from the reservoir 10 athrough the supply line 10 b into the separator 6.

The adjustable pumps 8 c, 10 c and 12 c and thus the flow rates of theincoming initial liquid medium 4, the incoming washing solution 18 andthe product liquid medium 4′ to be extracted can be controlledindependently, either manually or by means of a control unit 24 thatwill be described below.

The second outlet system 14 is adapted to extract waste 20, such as fat,debris, anticoagulants, damaged cells and excess washing solution, fromthe separator 6 during processing of the initial liquid medium 4. Thesecond outlet system 14 comprises a reservoir 14 a that is connected tothe separator 6 via an output line 14 b. The output line 14 b reachesthe spiral channel of the separator 6 preferably about 270° after itsinnermost end. In general, the output line 14 b can reach the spiralchannel anywhere between the position where the supply line 10 b reachesthe spiral channel and 360° after the innermost end of the spiralchannel. According to FIG. 1, the second outlet system 14 does notcomprise an adjustable pump. However, an adjustable pump can be providedthat is adapted to adjust the extraction rate of waste 20 from theseparator through the output line 14 b to the reservoir 14 a.

The device 2 further comprises a sensor 22 (e.g. an ultrasonic sensor oran optical sensor) adapted to measure a physical parameter related tothe initial concentration of the cells in the initial liquid medium 4 inthe first supply system 8. If the initial liquid medium 4 is blood, thesensor 22 might be adapted to measure the hematocrit value of the bloodor any related physical parameter (e.g. optical transparency, viscosity,density) from which the hematocrit can be deduced. The hematocrit valueof the incoming blood can fluctuate strongly, typically between 5 and70%. The hematocrit value can even be up to 85% depending on the timethe initial liquid medium 4 stays in the reservoir 8 a of the firstsupply system 8. Preferably, the sensor 22 is provided to measure thehematocrit value of the blood in the supply line 8 b between thereservoir 8 a and the pump 8 c of the first supply system 8 (upstream ofthe pump 8 c). The measurements are performed periodically, e.g. every5-10 s, the periodicity being adjustable.

Alternatively, the sensor 22 can be provided to measure the hematocritvalue of the blood in the reservoir 8 a of the first supply system 8 orin the supply line 8 b between the pump 8 c and the entrance of theseparator 6.

The control unit 24 is provided and configured to control at least oneprocess parameter of the device 2 such that the product concentration ofthe cells in the product liquid medium 4′ is within a predefinedconcentration range that can depend on national standards and customerrequirements. The hematocrit of the erythrocyte fraction 4′ ispreferably between 55 and 70% and more preferably between 60 and 65%.

To this end, the control unit 24 is coupled to the sensor 22 on the onehand and to the respective element of the device related to the processparameter on the other hand (as shown by dashed lines in FIG. 1). In theembodiment in FIG. 1, the respective element is the adjustable pump 10c. The physical parameter related to the concentration of the cells(hematocrit value) measured by the sensor 22 is used as an input signalfor the control unit 24 that generates an output signal as a function ofthe physical parameter measured by the sensor 22. This output signal isused to control the process parameter of the respective element of thedevice. The control unit 24 is thus adapted to control at least oneprocess parameter of the device 2 as a function of the physicalparameter measured by the sensor 22.

According to the embodiment shown in FIG. 1, the process parameterdetermines the flow rate of the washing solution 18 to the separator 6.The control unit 24 of FIG. 1 is thus coupled to the pump 10 c of thesecond supply system 10 and to the sensor 22.

According to another embodiment (not shown), the control unit 24 can beprovided to control several process parameters of the device 2simultaneously (or another process parameter than the flow rate of thewashing solution 18 to the separator 6). In addition (or as analternative) to the flow rate of the washing solution 18, furtherprocess parameters can determine the flow rate of the initial liquidmedium 4, the flow rate of the product liquid medium 4′ and/or therotational speed of the separator 6. Correspondingly, the control unit24 may be coupled to the pump 8 c of the first supply system 8, the pump12 c of the first outlet system 12 and/or the drive unit of theseparator 6.

In particular, the control unit 24 can be provided to controlsimultaneously several process parameters determining the flow rate ofthe washing solution 18, the flow rate of the initial liquid medium 4,the flow rate of the product liquid medium 4′ and the rotational speedof the separator 6. In general, the control unit 24 is configured toreduce the flow rate of the washing solution 18, the flow rate of theincoming blood and the rotational speed of the separator 6 and toincrease the flow rate of the erythrocyte fraction as the hematocritvalue increases. In Table I, an example of the relationship between thehematocrit value and the different process parameters is shown for adevice comprising a separator 6 in the form of a rotating separatorchamber of the Fresenius Kabi autotransfusion set AT for the continuousautotransfusion system C.A.T.S. described e.g. by G. Shulman in TheJournal Of Extra-Corporeal Technology, Vol. 32, Nr. 1, March 2000, p.11-19. More specifically, Table I indicates flow ranges and values forthe usual operational conditions of the Fresenius Kabi spiral separationchamber. In general, the values will depend on the characteristics ofthe separator 6 used.

TABLE I Dependency of the process parameters on the hematocrit value ofthe incoming blood (revolutions per minute are abbreviated as rpm)hematocrit value flow rate of the flow rate of the of the incomingrotational flow rate of incoming blood erythrocyte blood (initial speedof the the washing (initial liquid fraction (product liquid medium 4)separator solution medium 4) liquid medium 4′) [%] [rpm] [ml/min][ml/min] [ml/min] <15 >2200 normal, i.e. >150  5-25 >100 15-30 2100normal, i.e. >100  25-100 >100 30-45 1900 slightly >100 100-160 reduced,85-90% of the normal value 45-55 <1900 Reduced, 55-85% >20 160-190 ofthe normal value >55 <1900 extremely <10 160-190 reduced, 30-55% of thenormal value

Alternatively, a centrifuge chamber as described in US 2013/0310241 A1,a disposable centrifuge bowl as described in U.S. Pat. No. 4,943,273, aLatham bowl as described in EP 0 799 645 B1, a C4 dual stage separationchamber as described by T. Zeiler and V. Kretschmer in lnfus. Ther.Transfus. Med., Vol 27, Nr. 3, 2000, p. 119-126 and by E. F. Strasser etal. in Transfusion. Vol. 46, January 2006, p. 66-73 or a rotary membraneseparation device as described in EP 0 527 973 B1 may be used in thedevice 2. The concept of variation and process parameter interactions issimilar for all these types of separation chambers but the absolutevalues of the relevant parameters may differ.

FIG. 2 shows a second embodiment, which differs from the firstembodiment essentially by the position of the sensor 22′. According tothe second embodiment, the sensor 22′ is provided between the pump 12 cof the first outlet system 12 and the separator 6 (upstream of the pump12 c) and adapted to measure a physical parameter related to the productconcentration of the cells in the product liquid medium 4′ in the firstoutlet system 12. Alternatively, the sensor 22′ can be provided tomeasure a physical parameter related to the product concentration of thecells in the product liquid medium in the reservoir 12 a of the firstoutlet system 12 or in the output line 12 b between the pump 12 c andthe reservoir 12 a. If the product liquid medium 4′ is formed by theerythrocyte fraction of the blood fed into the separator 6, then thesensor 22′ (e.g. an ultrasonic sensor or an optical sensor) may beadapted to measure the hematocrit value or a physical parameter relatedto the hematocrit value of the erythrocyte fraction. In this case, thesensor 22′ has to be adapted to measure an elevated hematocrit value(between 50 and 90%) of the erythrocyte fraction. The measurements areperformed periodically, e.g. every 5-10 s, the periodicity beingadjustable.

Further, the sensor 22′ measuring the hematocrit value of theerythrocyte fraction can serve for quality management. To this end, thehematocrit value can be measured throughout the entire blood processingtreatment. Integration of the hematocrit value over time (in particularthe time interval of the entire blood processing treatment) leads thento the total red cell content of the entire erythrocyte fraction in thereservoir 12 a of the first outlet system 12. The total red cell contentdivided by the volume measured by the pump 12 c results in the totalaverage hematocrit of the erythrocyte product in the reservoir 12 a.

Also the sensor 22 of the first embodiment measuring the hematocritvalue of the blood to be processed can serve for determining the totalred cell content of the blood to be processed.

The physical parameter related to the initial or product concentrationof the cells can be graphically illustrated as a function of time inorder to simplify the analysis of the processing treatment, thecomposition of the initial liquid medium 4 and the composition of theproduct liquid medium 4′.

According to a third embodiment shown in FIG. 3, the device 2 comprisestwo sensors 22, 22′. The first sensor 22 is adapted to measure aphysical parameter related to the initial concentration of the cells inthe initial liquid medium 4 in the first supply system 8. The secondsensor 22′ is adapted to measure a physical parameter related to theproduct concentration of the cells in the product liquid medium 4′ inthe first outlet system 12. Preferably the sensors 22, 22′ are providedin the first supply system 8 and in the first outlet system 12 upstreamof the corresponding pumps 8 c, 12 c, respectively. Alternatively, thesensors 22, 22′ can be provided anywhere else in the first supply sytem8 and the first outlet system 12, respectively.

Both sensors 22, 22′ are coupled to the control unit 24 as shown bydashed lines in FIG. 3 and the physical parameters measured by thesensors 22, 22′ are used as input signals for the control unit 24 thatgenerates an output signal as a function of the physical parametersmeasured by the sensors 22 and 22′. The first sensor 22 monitors thehematocrit value of the initial liquid medium 4 in analogy to the sensor22 in the first embodiment (FIG. 1). The second sensor 22′ monitors thehematocrit value of the product liquid medium 4′ and thus the effect ofthe control that is based on the measurements of the first sensor 22.The second sensor 22′ may provide an instantaneous feedback to thecontrol unit 24 in order to further modify the process parameters of thedevice 2 if necessary.

The use of said two sensors 22, 22′ allows to determine the total redcell content of the blood to be processed and the total red cell contentof the entire erythrocyte fraction in the reservoir 12 a of the firstoutlet system 12, as already outlined for the first and secondembodiment. The use of said two sensors 22, 22′ further allows tocalculate the yield (also known as efficiency, yield rate, collectionrate, recovery, recovery rate or effectiveness) of cells afterprocessing the initial liquid medium in the device 2 on the basis of thefollowing equation:

${{yield}\mspace{11mu}\lbrack\%\rbrack} = {\frac{{V_{{product}\mspace{14mu} {liquid}\mspace{14mu} {medium}} \cdot {product}}\mspace{14mu} {{concentration} \cdot 100}}{{V_{{initial}\mspace{14mu} {liquid}\mspace{14mu} {medium}} \cdot {initial}}\mspace{14mu} {concentration}}.}$

The control unit 24 of the third embodiment is configured to control theflow rate of the washing solution 18 to the separator 6 and is thuscoupled to the pump 10 c of the second supply system 10, as shown inFIG. 3.

In analogy to the embodiments shown in FIGS. 1 and 2, the control unit24 can also be configured to control several process parameters of thedevice 2 simultaneously (or another process parameter than the flow rateof the washing solution 18 to the separator 6). In addition (or as analternative) to the flow rate of the washing solution 18, the processparameters can determine the flow rate of the initial liquid medium 4,the flow rate of the product liquid medium 4′ and/or the rotationalspeed of the separator (centrifuge) 6. Correspondingly, the control unit24 may also be coupled to the pump 8 c of the first supply system 8, thepump 12 c of the first outlet system 12 and/or the drive unit of theseparator 6.

In particular, the control unit 24 can be provided to controlsimultaneously several process parameters determining the flow rate ofthe washing solution 18, the flow rate of the initial liquid medium 4,the flow rate of the product liquid medium 4′ and the rotational speedof the separator 6.

In case of a defect of one of the two sensors 22, 22′, the device 2 isable to continue operation with the remaining sensor.

For in vitro processing of an initial liquid medium 4 comprising cellsin an initial concentration in order to obtain a product liquid medium4′ comprising cells in a product concentration, the device 2 can be usedto obtain a product liquid medium 4′ with a predetermined productconcentration of cells or with a maximum product concentration of cells.Below, the method shall be described using blood as an initial liquidmedium 4 that shall be processed to obtain the erythrocyte fraction ofthe blood as a product liquid medium 4′.

First, the reservoir 8 a of the first supply system is (partially)filled with a predetermined amount (e.g. more than 100 ml) of blood andthe reservoir 10 a of the second supply system is filled with a washingsolution 18, such as a physiologic saline solution, a cell culturemedium, plasma, albumin or the like, for washing purposes duringprocessing. The blood is transferred with a defined flow rate from thereservoir 8 a into the separator 6 via the pump 8 c of the first supplysystem 8. Before passing said pump 8 c, the hemotocrit of the blood or aphysical parameter related to the hematocrit allowing for itscalculation is measured by a sensor 22. The value measured by the sensor22 is transmitted to the control unit 24 and is used to determine acontrol signal as a function of the measured value according to therelationship shown in Table I. The control signal is used to control oneor more process parameters that may be chosen from the flow rate of thewashing solution 18, the flow rate of the initial liquid medium 4, theflow rate of the product liquid medium 4′ and/or the rotational speed ofthe separator 6. In particular, the control unit 24 reduces the flowrate of the washing solution 18, the flow rate of the incoming blood andthe rotational speed of the separator 6 and increases the flow rate ofthe erythrocyte fraction as the hematocrit value increases.

In the separation chamber 16 of the separator 6, the blood is subject toa first separation phase. The rotational speed of the separator 6depends on the hematocrit determined for the incoming blood by sensor22. In this phase, the blood is enriched to a hematocrit ofapproximately 80%. Plasma, fat, debris, anticoagulants or damaged cellsare washed out via the second outlet system 14 and are collected in thereservoir 14 a of the second outlet system 14.

In a subsequent washing phase, the washing solution 18 is added to theseparation chamber 16 in order to resuspend the erythrocytes that arepresent in the enriched blood. Residual plasma, fat, debris,anticoagulants or damaged cells are washed out via the second outletsystem 14.

After the washing phase, the partially processed blood is subject to asecond separation phase during which the washing solution 18 is washedout by centrifugation. The erythrocytes are packed to a hematocrit of 60to 65° A and the erythrocyte fraction is separated out via the firstoutlet system 12 and is collected in the reservoir 12 a of the firstoutlet system 12.

Optionally, the hematocrit of the erythrocyte fraction can be determinedby a second sensor 22′ located between the separator 6 and the reservoir12 a. The hematocrit value of the erythrocyte fraction can serve forinformation purposes. Additionally, the hematocrit of the erythrocytefraction (or a physical parameter related to the hematocrit) can be usedto control one or more process parameters of the device by means of thecontrol unit 24.

Although the device and method for processing an initial liquid mediumcomprising cells in an initial concentration in order to obtain aproduct liquid medium comprising cells in a product concentration havebeen examplarily described for blood as the initial liquid medium andits erythrocyte fraction as the product liquid medium, said device andmethod are not limited to these substances. They can also be employed toseparate stem cells from a nutrient solution, or to separate othercellular blood constituents than erythrocytes from blood, or to separatedifferent cell types from one another.

1. A device for processing an initial liquid medium comprising cells inan initial concentration in order to obtain a product liquid mediumcomprising cells in a product concentration, the device comprising: aseparator adapted to separate the initial liquid medium into variousconstituents, a first supply system for supplying the initial liquidmedium to the separator, a first outlet system for extracting theproduct liquid medium from the separator, a sensor adapted to measure aphysical parameter related to the concentration of the cells in theinitial or product liquid medium, a control unit coupled to the sensorand adapted to control at least one process parameter of the device as afunction of the physical parameter measured by the sensor, and a secondsupply system for supplying a solution to the separator with a givenflow rate wherein the flow rate of the solution in the second supplysystem during its supply to the separator is determined based on the atleast one process parameter.
 2. The device according to claim 1, whereinthe control unit is configured to reduce the flow rate of the solutionin the second supply system when the concentration of the cells measuredin the initial liquid medium increases.
 3. The device according to claim1, wherein the at least one process parameter determines the flow rateof the initial liquid medium in the first supply system during itssupply to the separator and/or the flow rate of the product liquidmedium in the first outlet system during its extraction from theseparator.
 4. The device according to claim 3, wherein the control unitis configured to control the flow rate of the initial liquid medium suchthat it is indirectly proportional to the initial concentration of thecells in the initial liquid medium in the first supply system and/or theflow rate of the product liquid medium such that it is directlyproportional to the initial concentration of the cells in the initialliquid medium in the first supply system.
 5. The device according toclaim 1, wherein the separator is a centrifuge.
 6. The device accordingto claim 5, wherein the control unit is configured to control arotational speed of the centrifuge based on the at least one processparameter such that the rotational speed is indirectly proportional tothe initial concentration of the cells in the initial liquid medium inthe first supply system.
 7. The device according to claim 1, wherein thefirst supply system comprises a supply line through which the initialliquid medium flows into the separator and in that the sensor is adaptedto measure a physical parameter related to the initial concentration ofthe cells in the initial liquid medium that is present in the supplyline of the first supply system.
 8. The device according to claim 1,wherein the first outlet system comprises an output line through whichthe product liquid medium flows out of the separator and the sensor isadapted to measure a physical parameter related to the productconcentration of the cells in the product liquid medium that is presentin the output line of the first outlet system.
 9. The device accordingto claim 1, wherein the control unit is configured to control the atleast one process parameter of the device such that the productconcentration of the cells in the product liquid medium is within apredefined concentration range.
 10. The device according to claim 1,wherein the control unit is configured to control the at least oneprocess parameter of the device such as to maximize the productconcentration of the cells in the product liquid medium.
 11. The deviceaccording to claim 1, wherein the device is configured to operate invitro.
 12. The device according to claim 1, further comprising a firstsensor adapted to measure a physical parameter related to theconcentration of the cells in the initial liquid medium and a secondsensor adapted to measure a physical parameter related to theconcentration of the cells in the product liquid medium.
 13. A methodfor processing an initial liquid medium comprising cells in an initialconcentration in order to obtain a product liquid medium comprisingcells in a product concentration, the method comprising the followingsteps: supplying the initial liquid medium to a separator via a firstsupply system, in the separator, separating the initial liquid mediuminto various constituents such as to obtain the product liquid medium,extracting the product liquid medium from the separator via a firstoutlet system, measuring a physical parameter related to theconcentration of the cells in the initial or product liquid medium usinga sensor, and controlling at least one process parameter as a functionof the physical parameter measured by the sensor wherein during the stepof separating the initial liquid medium into various constituents, asolution is supplied to the separator at a given flow rate via a secondsupply system wherein the flow rate of the solution in the second supplysystem during its supply to the separator is determined based on the atleast one process parameter.
 14. The method according to claim 13,wherein the method is carried out using the device according to claim 1.15. The method according to claim 13, wherein the liquid medium is bloodcomprising blood cells.